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891.
This review continues a general presentation of the metabolism of drugs and other xenobiotics started in a recent issue of Chemistry & Biodiversity. This Part 2 presents the numerous oxidoreductases involved, their nomenclature, relevant biochemical properties, catalytic mechanisms, and the very diverse reactions they catalyze. Many medicinally, environmentally, and toxicologically relevant examples are presented and discussed. Cytochromes P450 occupy a majority of the pages of Part 2, but a large number of relevant oxidoreductases are also considered, e.g., flavin-containing monooxygenases, amine oxidases, molybdenum hydroxylases, peroxidases, and the innumerable dehydrogenases/reductases. 相似文献
892.
A conceptual framework is developed and used for improving the livelihood of Sub-Saharan communities faced with multiple stresses
resulting from adverse environments, vector-transmitted diseases, and limited food. Ecosocial systems are the units for management.
The accumulation of ecological, economic, and social capital is the objective of management, the reduction of maintenance
costs is the key strategy, and technologies must satisfy ecological, economic, and social criteria. Interacting social system
components are communities, facilitators, scientists, and political as well as administrative organizations. An adaptive approach
to management allows flexibility in human and financial resource allocation and results in changes in knowledge and efficacy
of management operations. The implementation strategy at two sites in Ethiopia relies on a two-stage procedure. In Stage 1,
human and cattle health management set the conditions for development. In Stage 2, the ecosocial system is kept on a trajectory
to enhanced ecological, economic, and social capital. In each stage, the assignment of responsibilities leads to four implementation
phases. In Stage 1, successful precision targeting of tsetse and drug-based Trypanosoma spp. control increased the economic and social capital at the Luke site in southwestern Ethiopia but threatened the ecological
capital because of overstocking and land degradation. In Stage 2, a women’s group living in the outskirts of Addis Ababa (Ethiopia)
transformed barren land into a horticultural enterprise to enhance ecosystem service provision, including production of horticultural
goods, and increase soil fertility expressed by nutrients and water availability. This article reviews concepts on human livelihood
improvement in Sub-Saharan Africa and identifies principles that became important during project execution. 相似文献
893.
Grossmann J Fischer B Baerenfaller K Owiti J Buhmann JM Gruissem W Baginsky S 《Proteomics》2007,7(23):4245-4254
We present and evaluate a strategy for the mass spectrometric identification of proteins from organisms for which no genome sequence information is available that incorporates cross-species information from sequenced organisms. The presented method combines spectrum quality scoring, de novo sequencing and error tolerant BLAST searches and is designed to decrease input data complexity. Spectral quality scoring reduces the number of investigated mass spectra without a loss of information. Stringent quality-based selection and the combination of different de novo sequencing methods substantially increase the catalog of significant peptide alignments. The de novo sequences passing a reliability filter are subsequently submitted to error tolerant BLAST searches and MS-BLAST hits are validated by a sampling technique. With the described workflow, we identified up to 20% more groups of homologous proteins in proteome analyses with organisms whose genome is not sequenced than by state-of-the-art database searches in an Arabidopsis thaliana database. We consider the novel data analysis workflow an excellent screening method to identify those proteins that evade detection in proteomics experiments as a result of database constraints. 相似文献
894.
895.
Deletion of complement factor H-related genes CFHR1 and CFHR3 is associated with atypical hemolytic uremic syndrome
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Zipfel PF Edey M Heinen S Józsi M Richter H Misselwitz J Hoppe B Routledge D Strain L Hughes AE Goodship JA Licht C Goodship TH Skerka C 《PLoS genetics》2007,3(3):e41
Atypical hemolytic uremic syndrome (aHUS) is associated with defective complement regulation. Disease-associated mutations have been described in the genes encoding the complement regulators complement factor H, membrane cofactor protein, factor B, and factor I. In this study, we show in two independent cohorts of aHUS patients that deletion of two closely related genes, complement factor H-related 1 (CFHR1) and complement factor H-related 3 (CFHR3), increases the risk of aHUS. Amplification analysis and sequencing of genomic DNA of three affected individuals revealed a chromosomal deletion of approximately 84 kb in the RCA gene cluster, resulting in loss of the genes coding for CFHR1 and CFHR3, but leaving the genomic structure of factor H intact. The CFHR1 and CFHR3 genes are flanked by long homologous repeats with long interspersed nuclear elements (retrotransposons) and we suggest that nonallelic homologous recombination between these repeats results in the loss of the two genes. Impaired protection of erythrocytes from complement activation is observed in the serum of aHUS patients deficient in CFHR1 and CFHR3, thus suggesting a regulatory role for CFHR1 and CFHR3 in complement activation. The identification of CFHR1/CFHR3 deficiency in aHUS patients may lead to the design of new diagnostic approaches, such as enhanced testing for these genes. 相似文献
896.
897.
Unsupervised fluorescence lifetime imaging microscopy for high content and high throughput screening
Proteomics and cellomics clearly benefit from the molecular insights in cellular biochemical events that can be obtained by advanced quantitative microscopy techniques like fluorescence lifetime imaging microscopy and F?rster resonance energy transfer imaging. The spectroscopic information detected at the molecular level can be combined with cellular morphological estimators, the analysis of cellular localization, and the identification of molecular or cellular subpopulations. This allows the creation of powerful assays to gain a detailed understanding of the molecular mechanisms underlying spatiotemporal cellular responses to chemical and physical stimuli. This work demonstrates that the high content offered by these techniques can be combined with the high throughput levels offered by automation of a fluorescence lifetime imaging microscope setup capable of unsupervised operation and image analysis. Systems and software dedicated to image cytometry for analysis and sorting represent important emerging tools for the field of proteomics, interactomics, and cellomics. These techniques could soon become readily available both to academia and the drug screening community by the application of new all-solid-state technologies that may results in cost-effective turnkey systems. Here the application of this screening technique to the investigation of intracellular ubiquitination levels of alpha-synuclein and its familial mutations that are causative for Parkinson disease is shown. The finding of statistically lower ubiquitination of the mutant alpha-synuclein forms supports a role for this modification in the mechanism of pathological protein aggregation. 相似文献
898.
Leamey CA Merlin S Lattouf P Sawatari A Zhou X Demel N Glendining KA Oohashi T Sur M Fässler R 《PLoS biology》2007,5(9):e241
Binocular vision requires an exquisite matching of projections from each eye to form a cohesive representation of the visual world. Eye-specific inputs are anatomically segregated, but in register in the visual thalamus, and overlap within the binocular region of primary visual cortex. Here, we show that the transmembrane protein Ten_m3 regulates the alignment of ipsilateral and contralateral projections. It is expressed in a gradient in the developing visual pathway, which is consistently highest in regions that represent dorsal visual field. Mice that lack Ten_m3 show profound abnormalities in mapping of ipsilateral, but not contralateral, projections, and exhibit pronounced deficits when performing visually mediated behavioural tasks. It is likely that the functional deficits arise from the interocular mismatch, because they are reversed by acute monocular inactivation. We conclude that Ten_m3 plays a key regulatory role in the development of aligned binocular maps, which are required for normal vision. 相似文献
899.
Shotgun proteomics uses liquid chromatography-tandem mass spectrometry to identify proteins in complex biological samples. We describe an algorithm, called Percolator, for improving the rate of confident peptide identifications from a collection of tandem mass spectra. Percolator uses semi-supervised machine learning to discriminate between correct and decoy spectrum identifications, correctly assigning peptides to 17% more spectra from a tryptic Saccharomyces cerevisiae dataset, and up to 77% more spectra from non-tryptic digests, relative to a fully supervised approach. 相似文献
900.
Although three-dimensional electron microscopy (3D-EM) permits structural characterization of macromolecular assemblies in distinct functional states, the inability to classify projections from structurally heterogeneous samples has severely limited its application. We present a maximum likelihood-based classification method that does not depend on prior knowledge about the structural variability, and demonstrate its effectiveness for two macromolecular assemblies with different types of conformational variability: the Escherichia coli ribosome and Simian virus 40 (SV40) large T-antigen. 相似文献